Impairment of sperm DNA methylation in male infertility: a meta‐analytic study
Impairment of sperm DNA methylation in male infertility: a meta‐analytic study
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DOI：
10.1111/andr.12379
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发表时间：
2017-07
期刊：
影响因子：
4.5
通讯作者：
D. Santi;S. Vincentis;E. Magnani;G. Spaggiari
中科院分区：
文献类型：
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作者：
D. Santi;S. Vincentis;E. Magnani;G. Spaggiari
考虑到辅助生殖技术(ART)的广泛应用，参与精子发生的特定基因的DNA甲基化越来越具有临床意义，这可能是医学辅助妊娠中与基因组印记相关的综合征发生率增加的原因。一些试验表明，男性亚生育能力和精子DNA甲基化之间存在关系，尽管它对精液参数变化的影响仍然存在争议。目的：评估精子印迹基因甲基化异常是否与精子参数受损有关。评估印记基因精子DNA甲基化的对照临床试验的荟萃分析比较特发性不育症男性与生育对照组。纳入24项研究，允许对H19、MEST、Snrpn和LINE-1进行荟萃分析评估。当结果显示高度异质性时，使用随机效应模型。879名不育男性精子H19甲基化水平显著低于562名生育男性(7.53%，95%CI：5.14-9.93%，p<；0.001)，提示不育男性精子DNA甲基化异常的风险比(95%CI：5.55-17.70，p<；0.001，I2=19%)高9.91倍。不育症患者的平均甲基化水平显著高于生育男性(3.35%，95%CI：1.41-5.29%，p<；0.001)，而SNRPN的平均甲基化水平显著高于对照组(3.23%，95%CI：0.75-5.72%，p<；0.001)。LINE-1甲基化水平在男性不育症患者和对照人群中差异无统计学意义(0.44%，95%CI：−2.04-1.16%，p=0.63)。荟萃分析方法表明，男性不育与精子H19、MEST和Snrpn基因甲基化改变有关。尽管精子DNA甲基化在不育症中的作用尚不清楚，但精子DNA甲基化可能与ART的表观遗传风险有关。在这种情况下，在临床实践中提出这项分析之前，应该在特别的前瞻性研究中评估对最具代表性的基因的准确识别和成本效果评估。
Considering the widespread use of assisted reproductive techniques (ART), DNA methylation of specific genes involved in spermatogenesis achieves increasingly clinical relevance, representing a possible explanation of increased incidence of syndromes related to genomic imprinting in medically assisted pregnancies. Several trials suggested a relationship between male sub‐fertility and sperm DNA methylation, although its weight on seminal parameters alteration is still a matter of debate. To evaluate whether aberrant sperm DNA methylation of imprinted genes is associated with impaired sperm parameters. Meta‐analysis of controlled clinical trials evaluating imprinted genes sperm DNA methylation comparing men with idiopathic infertility to fertile controls. Twenty‐four studies were included, allowing a meta‐analytic evaluation for H19, MEST, SNRPN, and LINE‐1. When a high heterogeneity of the results was demonstrated, the random effect model was used. H19 methylation levels resulted significantly lower in 879 infertile compared with 562 fertile men (7.53%, 95% CI: 5.14–9.93%, p < 0.001), suggesting a 9.91‐fold higher risk ratio to show aberrant sperm DNA methylation (95% CI: 5.55–17.70, p < 0.001, I2 = 19%) in infertile men. The mean MEST methylation level was significantly higher in 846 infertile compared with 353 fertile men (3.35%, 95% CI: 1.41–5.29%, p < 0.001), as well as for SNRPN comparing 301 infertile men with 124 controls (3.23%, 95% CI: 0.75–5.72%, p < 0.001). LINE‐1 methylation levels did not differ between 291 infertile men and 198 controls (0.44%, 95% CI: −2.04–1.16%, p = 0.63). The meta‐analytic approach demonstrated that male infertility is associated with altered sperm methylation at H19, MEST, and SNRPN. Although its role in infertility remains unclear, sperm DNA methylation could be associated with the epigenetic risk in ART. In this setting, before proposing this analysis in clinical practice, an accurate identification of the most representative genes and a cost‐effectiveness evaluation should be assessed in ad hoc prospective studies.